K1-70 - A Study in Subjects With Graves' Disease

NCT02904330 | Completed Phase 1 DMC

• 1 other identifier: K1im001
• Study Type: interventional
• Target: 18
• Locations: 1 country
• Sites: 2

Brief Summary

This study is the first time that K1-70 will be administered to humans. The principal aim of this study is to obtain safety and tolerability data when K1-70 is administered as an IM injection or as an IV infusion to subjects with Graves' disease. Current therapy for Graves' disease includes treatment with anti-thyroid drugs, destruction of the thyroid using radioiodine, or total surgical thyroidectomy. Beta-blockers and calcium antagonists may be used to control some of the symptoms of hyperthyroidism. K1-70 is a thyroid stimulating hormone receptor antagonist that may provide new in vivo diagnostic and therapeutic tools for the management of patients with Graves' disease, patients with thyroid cancer and patients who would benefit from controlling receptor activity.

Conditions

Graves' Disease

Outcome Measures

Primary Outcomes (1)

• Safety and tolerability will be measured using vital signs, ECG, blood samples for haematology, coagulation, clinical biochemistry and hormone panel, urinalysis, eye examinations, physical examinations and examination of injection or infusion site.

  Safety and tolerability testing consists of vital signs, ECG, blood samples for haematology, coagulation, clinical biochemistry and hormone panel, urine samples for urinalysis, eye examinations, physical examinations and examination of injection or infusion site. All clinically significant results and the number of treatment related adverse events will be reported.

  Over a period of 18 weeks

Secondary Outcomes (11)

• The concentration of K1-70 drug in the blood will be measured over time.

  Over a period of 18 weeks

• The concentration of K1-70 drug in the blood will be measured over time.

  Over a period of 18 weeks

• The concentration of K1-70 drug in the blood will be measured over time.

  Over a period of 18 weeks

• The concentration of K1-70 drug in the blood will be measured over time.

  Over a period of 18 weeks

• The concentration of K1-70 drug in the blood will be measured over time.

  Over a period of 18 weeks

Other Outcomes (4)

• Exploratory Objective: Thyroid hormones will be measured over time and their correlation to baseline TSH receptor autoantibody (TRAb) levels will be reported at different time points

  Over a period of 18 weeks

• Exploratory Objective: Thyroid hormones will be measured over time and their correlation to baseline TSH receptor autoantibody (TRAb) levels will be reported at different time points

  Over a period of 18 weeks

• Exploratory Objective: Thyroid hormones will be measured over time and their correlation to baseline TSH receptor autoantibody (TRAb) levels will be reported at different time points

  Over a period of 18 weeks

Study Arms (1)

Single dose

EXPERIMENTAL

The intervention is K1-70 intramuscular or K1-70 intravenous. This is a single, ascending, intramuscular or intravenous dose, sequential group study.

Drug: K1-70 intramuscular or K1-70 intravenous

Interventions

K1-70 intramuscular or K1-70 intravenous DRUG

Each subject will receive one dose of K1-70 by IM injection or one dose of K1-70 by IV infusion on the morning of Day 1.

Single dose

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• age 18-75 years
• have Graves' disease and are being treated with anti-thyroid medications OR not treated with anti-thyroid medications (due to side-effects) and who are clinically and biochemically euthyroid or hyperthyroid
• have a body mass index (weight \[kg\]/height \[m\]2) between 18.5 and 35.0 kg/m2

You may not qualify if:

• current or chronic history of liver disease
• history of cancer within the last 5 years except localised skin cancer
• Graves' orbitopathy with clinical activity score \>3/7
• evidence of optic neuropathy and/or corneal breakdown
• significant systemic infection
• history of recurrent or current infection
• splenectomy
• recently had major surgery or plan major surgery
• had thromboembolic event due to a blood clot in the last 12 months
• have clinically significant laboratory tests
• a clinically significant allergic condition (excluding hay fever)
• currently receiving corticosteroids
• smoke more than 10 cigarettes (or its equivalent in nicotine (including use of e-cigarettes)) per day
• history of drug abuse

Sponsors & Collaborators

• AV7 Limited: lead

Study Sites (2)

Royal Liverpool University Hospital Clinical Research Unit

Liverpool, L7 8XP, United Kingdom

Location

Medicines Evaluation Unit

Manchester, M23 9QZ, United Kingdom

Location

Related Publications (3)

• Evans M, Sanders J, Tagami T, Sanders P, Young S, Roberts E, Wilmot J, Hu X, Kabelis K, Clark J, Holl S, Richards T, Collyer A, Furmaniak J, Smith BR. Monoclonal autoantibodies to the TSH receptor, one with stimulating activity and one with blocking activity, obtained from the same blood sample. Clin Endocrinol (Oxf). 2010 Sep;73(3):404-12. doi: 10.1111/j.1365-2265.2010.03831.x. Epub 2010 Jun 9.

  PMID: 20550534 BACKGROUND

• Sanders P, Young S, Sanders J, Kabelis K, Baker S, Sullivan A, Evans M, Clark J, Wilmot J, Hu X, Roberts E, Powell M, Nunez Miguel R, Furmaniak J, Rees Smith B. Crystal structure of the TSH receptor (TSHR) bound to a blocking-type TSHR autoantibody. J Mol Endocrinol. 2011 Feb 15;46(2):81-99. doi: 10.1530/JME-10-0127. Print 2011 Apr.

  PMID: 21247981 BACKGROUND

• Furmaniak J, Sanders J, Young S, Kabelis K, Sanders P, Evans M, Clark J, Wilmot J, Rees Smith B. In vivo effects of a human thyroid-stimulating monoclonal autoantibody (M22) and a human thyroid-blocking autoantibody (K1-70). Auto Immun Highlights. 2011 Sep 14;3(1):19-25. doi: 10.1007/s13317-011-0025-9. eCollection 2012 Apr.

  PMID: 26000124 BACKGROUND

MeSH Terms

Conditions

Graves Disease

Condition Hierarchy (Ancestors)

Exophthalmos; Orbital Diseases; Eye Diseases; Goiter; Thyroid Diseases; Endocrine System Diseases; Hyperthyroidism; Autoimmune Diseases; Immune System Diseases

Study Officials

• Dave Singh, Professor

  Medicines Evaluation Unit, Manchester, UK

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: August 18, 2016
• First Posted: September 16, 2016
• Study Start: August 1, 2016
• Primary Completion: April 1, 2021
• Study Completion: April 1, 2021
• Last Updated: May 20, 2021

Record last verified: 2021-05

Data Sharing

• IPD Sharing: Will not share

Locations

GB (2)